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The Nature of Host Defenses
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There are at Least Three Lines of Defense Against Microbial Invasion
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1st line of defense – Non-Specific Barriers
intact skin mucous membranes & their secretions 2nd line of defense - Non-Specific phagocytic white blood cells inflammation -complement fever -interferon 3rd line of defense- Specific B & T lymphocytes antibodies nonspecific
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Physical or Anatomical Barriers
Cornefication of outermost layer of skin Flushing effect of sweat glands Rapid replacement of damaged cells Mucous impedes attachment & entry of bacteria Blinking & tear production Nasal hair traps larger particles
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Chemical Defenses Sebaceous secretions Lysozyme in tears
High lactic acid & electrolyte concentration in sweat Skin’s acidic pH Hydrochloric acid in stomach Digestive juices and bile of intestines Semen contains antimicrobial agents Vagina has acidic pH
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Genetic Defenses Some pathogens have great specificity
Some genetic differences exist in susceptibility
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A Healthy Immune System is Responsible for
Surveillance of the body Recognition of foreign material Destruction of entities deemed to be foreign
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Immune System Definitions
White blood cells (leukocytes) – have an innate ability to recognize and distinguish foreign material Non-self – foreign material Self – normal cells of the body Pathogen-associated patterns (PAMPs) – molecules shared by microorganisms Pathogen recognition receptors (PRRs) – receptors on WBCs for PAMPs
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The Immune System A large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue The four major subdivisions of immune system: Reticuloendothelial system (RES) Extracellular fluid (ECF) Bloodstream Lymphatic system
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Reticuloendothelial System (RES)
Network of connective tissue fibers that interconnects other cells and meshes with the connective tissue network surrounding organs Inhabited by phagocytic cells – mononuclear phagocyte system – macrophages ready to attack and ingest microbes that passed the first line of defense
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White Blood Cells (Leukocytes) are the Body’s Immune Cells
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Leukocytes Neutrophils % - lobed nuclei with lavender granules; phagocytes Eosinophils – 1-3% - orange granules & bilobed nucleus; destroy eucaryotic pathogens Basophils, mast cells – 0.5%; constricted nuclei, dark blue granules; release chemical mediators
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Leukocytes - Continued
Lymphocytes – 20-35% - large nucleus; B & T cells involved in the specific immune response Monocytes, macrophages – 3-7%- large nucleus; phagocytic
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Lymphatic System Provides an auxiliary route for return of extracellular fluid to the circulatory system Acts as a drain-off system for the inflammatory response Renders surveillance, recognition, and protection against foreign material
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Lymphatic Vessels Lymphatic capillaries permeate all parts of the body except the CNS Thin walls easily permeated by extracellular fluid which is then moved by contraction of skeletal muscles Functions to return lymph to circulation; flow is one-direction-toward the heart-eventually returning to blood stream
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Lymphatic Fluid Lymph is a plasmalike liquid carried by lymphatic circulation Formed when blood components move out of blood vessels into extracellular spaces Made up of water, dissolved salts, 2-5% proteins Transports white blood cells, fats, cellular debris & infectious agents
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Lymph Nodes Small, encapsulated, bean-shaped organs stationed along lymphatic channels & large blood vessels of the thoracic and abdominal cavities Contain populations of T and B lymphocytes in sinuses Act as sites for encounters with microbes leading to specific immune responses
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Actions of the Second Line of Defense
Recognition Inflammation Phagocytosis Interferon Complement
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Recognition Protein receptors within cell membrane of macrophages, called Toll-like receptors Detect foreign molecules and signal the macrophage to produce chemicals which: stimulate an inflammatory response (nonspecific) promote the activity of B and T cells (specific)
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Inflammation – a Generalized Response to Tissue Injury
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Stages of Inflammation
Blood vessels constrict, then dilate in response to chemical mediators and cytokines Edema swells tissues, helping prevent spread of infection WBC’s, microbes, debris and fluid collect to form pus Pyrogens (endogenous or exogenous) may induce fever Macrophages and neutrophils engage in phagocytosis
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Activities of Phagocytes
To survey tissue compartments & discover microbes, particulate matter & dead or injured cells To invade and eliminate these materials To extract immunogenic information from foreign matter
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Characteristics of Leukocytes
Diapedesis – migration of cells out of blood vessels into the tissues Chemotaxis – migration in response to specific chemicals at the site of injury or infection
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Phagocytosis
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Fever: Another Non-Specific Response
Elevated body temperature in response to a chemical mediator Inhibits temperature-sensitive microorganisms Impedes bacterial nutrition Stimulates immune reactions
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Interferon Small proteins produced by specific cells
Alpha interferon- lymphocytes & macrophages Beta interferon – fibroblasts & epithelial cells Gamma interferon – T cells Produced in response to viruses, RNA, immune products, and various antigens Bind to cell surfaces and induce expression of antiviral proteins Inhibit expression of cancer genes
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Complement Consists of 26 blood proteins that work in concert to destroy bacteria, fungi and enveloped viruses Complement proteins are activated by cleavage Classical pathway Alternative pathway
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Complement Pathways Classical pathway – activated by the presence of antibody bound to microorganism Alternative pathway – begins when complement proteins bind to normal cell wall and surface components of microorganisms
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Complement Uses a Cascade System
One component activates another which activates another, and so on
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Complement
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